Cell-free Fetal DNA in Maternal Serum (NIPT)

This is a new screening protocol for assessment of the likelihood of a mother having a fetus with Trisomy 21, Trisomy 18, Trisomy 13 or a fetus with a sex chromosome anomaly. 

The screening test has an excellent sensitivity for Trisomy 21.  The sensitivity for the other chromosome anomalies is not as good.  A patient who has a positive screen will need to have a diagnostic test to ensure that it is a true positive.  As well, with this new technology, there is the issue of false positives.

Some people have asked me about other screens that can be done, including micro deletion anomalies such as Di George syndrome or cri-du-chat, etc.  Because the incidence of these diseases and micro-deletions is very low, the positive predicted failure of these screening tests is too low.  This then, makes the analysis of many micro-deletions an impractical proposal, as more diagnostic tests, amniocentesis or CVS, would need to be done unnecessarily. 

I would suggest that patients can be divided into three groups.

  • If the patient has a risk for a chromosome anomaly of 1 : 2 to 1 : 100, a diagnostic test should be considered, such as amniocentesis.

  • If the risk is 1 : 100 to 1 : 1000, a cell-free DNA test could be offered. 

  • If the risk is less than 1 : 1000, no further testing needs to be done.

The first trimester assessment/nuchal translucency test was introduced in 1996 to try and target women who were at a high risk of aneuploidy by looking at the fetus rather than looking at the mother’s age.  Since then, the nuchal translucency test has been very successful in identifying fetal anomalies early.  It is now feasible to identify major cardiac anomalies at the 12 - 13 week scan and hence have an early echo-cardiogram.  As well, the first trimester test now is useful for assisting patients who are at high risk of developing early on-set pre-eclampsia, IUGR or early delivery.  Jon Hyatt has published a paper looking at addition of Aspirin for women of high risk of early onset pre-eclampsia.  He was able to show that there was a 9 to 10 time’s reduction in early onset pre-eclampsia by the addition of low-dose Aspirin prior to 16 weeks gestation.

There is the view that if a patient has cell-free fetal DNA screen, that she does not need a first trimester assessment.  This is a totally incorrect assumption.  If I had only one opportunity to scan a woman in pregnancy, it would be at the twelve week mark.